Catechol-containing molecules such as DOPA and dopamine are important compounds with widely useful effects as therapeutic agents. Acetonide-protected catechol-containing compounds such as DOPA and dopamine are useful in many applications, including Fmoc peptide synthesis and conjugating DOPA and dopamine with other small molecules, polymers, or macromolecules of interest.
DOPA.
The amino acid 3,4-dihydroxyphenylalanine (DOPA) (FIG. 1, 1) is found in a number of biological tissues, including the adhesive plaques of the marine mussel Mytilus edulis,1,2 the cement proteins of the sandcastle worm Phragmatopoma californica,3 squid beaks,4 and in the eggshell precursor proteins of Fasciola hepatica.5,6 The DOPA residues are thought to contribute to the bioadhesive and structural properties of these tissues.7-9 As a therapeutic, L-DOPA is commonly prescribed for the treatment of Parkinson's disease.10 
To facilitate the synthesis of DOPA-containing therapeutic compounds and biomimetic materials, it is necessary to properly protect the catechol side-chain of DOPA during chemical reactions. In the case of the synthesis of DOPA-containing peptides, solid phase peptide synthesis (SPPS) by Fmoc strategy is a preferred approach due to its convenience and efficiency.
Various protecting groups have been reported to protect the side-chain catechol group of DOPA residues, including cyclic ethyl orthoformate,11 TBDPS,12 and acetonide.13,14 The acetonide protecting group has proven to be compatible with the Fmoc SPPS method,15 but a synthetic route to Fmoc-DOPA(acetonide)-OH (7) has not been reported. Easy protection/deprotection together with good stability to strong bases and weak acids makes the acetonide protecting group especially useful.
One reported method to make H-DOPA(acetonide)-OH (6), from which Fmoc-DOPA(acetonide)-OH (7) may be synthesized, constructed the amino acid derivative from acetonide-protected 4-methylbenzene-1,2-diol in several steps leading to a racemic mixture of Fmoc-DOPA(acetonide)-OH.13 However, conventional methods of synthesis are complicated, multi-step processes that often require an additional step of chiral separation to obtain an optically pure product.
Dopamine.
As a member of the catecholamine family, 4-(2-aminoethyl)benzene-1,2-diol (dopamine) contains both amino and catechol moieties, each capable of a diversity of potential reactions and interactions. In both vertebrate and invertebrate animals, dopamine is the precursor of norepinephrine and epinephrine but also an important neurotransmitter itself, essential to the normal functioning of the central nervous system.33 Parkinson's disease, affecting about 1% of the senior population, is characterized by a reduction of dopamine levels in the striatum.10 At physiological pH dopamine is almost completely ionized, resulting in low permeation across the blood brain barrier and precluding it as a direct treatment for Parkinson's disease.
Conjugation to lipophilic molecules, such as docosahexaenoic acid (DHA), may assist dopamine's uptake by the brain. The prodrug DHA-dopamine29 was demonstrated to have a brain penetration index of 30%, comparable with that of D-glucose (33%). Catechols exhibit other important chemical properties including chelation of various metal ions and remarkable interfacial chemical properties.7 As a result, there is increasing interest in exploiting catechols and catechol derivatized polymers as surface coatings.30 Several recent reports describe the conjugation of dopamine to small molecule initiators and polymers, obtained through reaction of the amino group of dopamine to form a peptide bond.30,31. 
One of the challenges in conjugating dopamine is that it is readily oxidized, especially under basic conditions, to dopamine quinone, which undergoes self-polymerization or nucleophilic addition reactions with amino or sulfhydryl group.32 Proper protection of the catechol group is required during chemical modification of dopamine.
Direct protection of a catecholamine by acetonide is not easily accomplished by refluxing with acetone or its ketal 2,2-dimethoxypropane (DMP) in the presence of a catalyst, e.g., p-toluenesulfonic acid (TsOH). Such acetonide compounds as 1-(2,2-dimethylbenzo[1,3]dioxol-5-yl)propan-2-amine are usually obtained by a complicated method involving construction of the target molecule from an acetonide-protected catechol subunit, introduction of a nitro group by a nitration reagent such as nitroethane, and reduction of the —NO2 to —NH2 group with lithium aluminum hydride.36 One of the possible side reactions during direct acetonide protection of dopamine is that, as a beta phenylamine, dopamine readily undergoes Pictet-Spengler condensations with aldehydes and ketones to produce tetrahydroisoquinolines.37 Further, the conventional methods of producing acetonide-protected DOPA result in a racemic mixture, requiring additional costly and complicated purification steps.
Thus there is a need in the art for a simpler, cost-effective method for synthesizing acetonide-protected, catechol-containing compounds such as DOPA and dopamine.